[642] Morphologic and Molecular Analysis of Appendiceal Serrated Lesions: Colonic Terminology May Not Be Applicable

David Hernandez Gonzalo, Xiuli Liu, Deepa T Patil, Ana Bennett, Thomas P Plesec, John R Goldblum, Shih-Fan Kuan, Erinn Downs-Kelly, Bonnie Shadrach, Reetesh K Pai, Rish K Pai. Cleveland Clinic, Cleveland, OH; University of Pittsburgh Medical Center, Pittsburgh, PA

Background: Classification of serrated appendiceal lesions can be difficult, and it is unclear if pathologists should apply terminology used in the colon. SSP/As of the colon almost always have mutations in BRAF; however, a recent study found that some appendiceal sessile serrated polyps/adenomas (SSP/As) demonstrate KRAS mutations. The aim of this study was to analyze appendiceal lesions for KRAS and BRAF mutations and correlate mutational analysis with histologic features.
Design: We classified 94 appendiceal lesions using current standard terminology (hyperplastic polyp [HP], SSP/As, SSP/A with dysplasia, traditional serrated adenoma [TSA], tubular/tubulovillous adenoma [TA/TVA], and low-grade mucinous neoplasm [LAMN]). Lesions were also classified using a simplified scheme based on the presence of epithelial serrations and cytologic dysplasia: serrated non-dysplastic, serrated dysplastic, and dysplastic not-serrated. KRAS and BRAF mutational analysis was performed on isolated DNA via direct sequencing and allele specific PCR respectively.
Results: Using the simplified scheme, 32 cases were serrated non-dysplastic, 19 were serrated dysplastic, and 43 were dysplastic non-serrated. Based on standard terminology there were 9 HPs, 23 SSP/As, 9 SSP/As with dysplasia, 6 TSAs, 6 TA/TVA, and 41 LAMNs. BRAF mutationa were found in 4 of 70 cases (5.7%). However, KRAS mutations were found in 22 of 43 cases (51.1%) tested. The histologic classification of the 40 cases that were analyzed for both KRAS and BRAF mutations are shown in Table 1.

KRAS and BRAF mutations in Appendiceal lesions
Conventional terminologyKRAS mutatedBRAF mutatedKRAS/BRAF WT
HP (1)001 (100%)
SSP/A (9)8 (89%)1 (11%)0
SSP/A with dysplasia (7)4 (57%)2 (29%)1 (14%)
TSA (3)1 (33%)02 (67%)
TA/TVA (4)2 (50%)02 (50%)
LAMN (16)7 (44%)1 (6%)8 (50%)
Simplified terminology   
Serrated non-dysplastic (10)8 (80%)1 (10%)1 (10%)
Serrated dysplastic (13)7 (54%)2 (15%)4 (31%)
Dysplastic non-serrated (17)7 (41%)1 (6%)9 (53%)

Conclusions: Serrated lesions of the appendix that resemble SSP/As often harbor KRAS mutations, in stark contrast to the high percentage of BRAF mutations seen in SSP/As of the colon. These results indicate that the serrated pathway in the appendix may be different than the colon, and thus, colonic terminology may not be applicable to appendiceal lesions.
Category: Gastrointestinal

Wednesday, March 6, 2013 9:30 AM

Poster Session V # 116, Wednesday Morning


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